The Efficacy of Ketamine Therapy in the Treatment of Depression

Dr. Zaheer Aslam • May 22, 2024

Depression is a complex and often debilitating condition that affects millions of people worldwide. Despite the availability of various treatment options, including psychotherapy and traditional antidepressant medications, many individuals continue to struggle with persistent symptoms.


In recent years, ketamine therapy has emerged as a promising alternative for those who have not found relief through conventional treatments.


This blog post delves into the efficacy of ketamine therapy in treating depression, exploring its mechanisms, benefits, and potential risks.

Understanding Depression and Treatment Challenges

Before diving into ketamine therapy, it is crucial to understand the nature of depression and the challenges associated with its treatment. Depression is characterized by persistent feelings of sadness, hopelessness, and a lack of interest or pleasure in activities. It can also manifest as physical symptoms such as changes in appetite, sleep disturbances, and fatigue.


Traditional treatment options for depression typically include a combination of psychotherapy and antidepressant medications such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).


While these treatments can be effective for many people, they often take several weeks to start working and may not provide adequate relief for everyone. In fact, up to one-third of individuals with depression do not respond to traditional treatments, highlighting the need for alternative approaches.

What is Ketamine Therapy?

Ketamine is a dissociative anesthetic that has been used safely in medical settings for decades. Originally developed as an anesthetic in the 1960s, it has gained attention more recently for its potential to treat depression, especially in cases where other treatments have failed. Ketamine therapy involves administering the drug in controlled, clinical settings, typically through intravenous (IV) infusions or intranasal sprays.

Mechanisms of Action: How Ketamine Works

Ketamine's rapid antidepressant effects distinguish it from traditional antidepressants, which can take weeks to become effective. The exact mechanisms through which ketamine alleviates depressive symptoms are not yet fully understood, but several theories have been proposed:

1. NMDA Receptor Antagonism: Ketamine is known to block N-methyl-D-aspartate (NMDA) receptors in the brain, which are involved in regulating mood and cognition. By inhibiting these receptors, ketamine may help restore synaptic connections and promote neuroplasticity.

2. AMPA Receptor Activation: Some research suggests that ketamine's antidepressant effects may also involve the activation of alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors, leading to increased release of neurotransmitters like glutamate. This can enhance synaptic communication and improve mood.

3. mTOR Pathway Activation: Ketamine has been shown to activate the mammalian target of the rapamycin (mTOR) pathway, which plays a crucial role in cell growth and synaptic plasticity. Activation of this pathway may contribute to the rapid and sustained antidepressant effects of ketamine.

Clinical Evidence: Efficacy of Ketamine Therapy

A growing body of clinical research supports the efficacy of ketamine therapy in treating depression. Several studies have demonstrated its rapid antidepressant effects, often occurring within hours of administration. Notably, ketamine has shown promise in treating treatment-resistant depression (TRD), a condition where patients do not respond to at least two different antidepressant medications.

Key Studies and Findings:

1. Berman et al. (2000): One of the earliest studies on ketamine's antidepressant effects, this randomized, placebo-controlled trial found that a single IV infusion of ketamine significantly reduced depressive symptoms within 72 hours compared to a placebo.

2. Zarate et al. (2006): This study further demonstrated ketamine's rapid and robust antidepressant effects in patients with TRD. Participants experienced significant improvements in depressive symptoms within 24 hours of a single infusion, with some effects lasting up to a week.

3. Murrough et al. (2013): In a larger, randomized controlled trial,  ketamine was found to be more effective than the active placebo midazolam in reducing depressive symptoms in patients with TRD. Approximately 64% of participants responded to ketamine, compared to 28% for midazolam.

4. Esketamine Nasal Spray:  In 2019, the U.S. Food and Drug Administration (FDA) approved esketamine, a derivative of ketamine, for use in conjunction with an oral antidepressant for adults with TRD. Clinical trials showed that esketamine nasal spray significantly improved depressive symptoms compared to a placebo.

Benefits of Ketamine Therapy

The potential benefits of ketamine therapy for depression are numerous:

1. Rapid Onset of Action: Unlike traditional antidepressants, which can take weeks to show effects, ketamine often produces noticeable improvements within hours or days.

2. Efficacy in Treatment-Resistant Cases: Ketamine has shown efficacy in individuals who have not responded to other treatments, offering hope for those with TRD.

3. Reduction in Suicidal Ideation: Several studies have found that ketamine can rapidly reduce suicidal thoughts, making it a valuable option for individuals at high risk of suicide.

4. Sustained Effects: While the immediate effects of ketamine may last only a few days to a week, repeated infusions or maintenance treatments can provide longer-lasting relief.

Potential Risks and Side Effects

Despite its promising benefits, ketamine therapy is not without risks and side effects. Some potential concerns include:

1. Dissociation and Hallucinations: Ketamine can induce dissociative states and hallucinations, which may be distressing for some individuals. These effects are typically short-lived and subside shortly after the infusion.

2. Potential for Abuse: As a Schedule III controlled substance, ketamine has a potential for abuse and addiction. However, when administered in a controlled, clinical setting, the risk is minimized.

3. Cardiovascular Effects: Ketamine can cause increases in blood pressure and heart rate, which may be problematic for individuals with certain cardiovascular conditions.

4. Long-Term Safety: While short-term studies have demonstrated ketamine's safety, the long-term effects of repeated ketamine use are not yet fully understood.

Conclusion: A Promising Future for Depression Treatment

Ketamine therapy represents a groundbreaking advancement in the treatment of depression, particularly for individuals who have not found relief through traditional methods. Its rapid onset of action, efficacy in treatment-resistant cases, and potential to reduce suicidal ideation make it a valuable addition to the arsenal of depression treatments.


However, it is essential to approach ketamine therapy with caution, considering the potential risks and side effects. As research continues to evolve, we can expect to gain a deeper understanding of ketamine's mechanisms and long-term safety, paving the way for more widespread and informed use.


If you or someone you know is struggling with depression and traditional treatments have not been effective, ketamine therapy may offer a glimmer of hope. Always consult with a qualified healthcare professional to determine the best course of action for your specific needs.

Take the Next Step with SW Florida TMS & Ketamine

Having the right treatment options and support system is crucial when fighting a battle against depression. At SW Florida TMS & Ketamine, we are here to help you fight the battle against depression and other mental health issues such as anxiety, OCD, PTSD, and more.


We use traditional modern methods to treat these health problems and will derive a treatment plan best suited to your condition. You can reach us at (239) 935-5599 or fill out our contact form to learn more about our treatment options. Don’t worry, you are not alone!

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Knowing that you are not alone is of utmost importance. Seek assistance for depression today!

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By Matt Rodriguez July 8, 2025
At-home ketamine therapy gained popularity during the pandemic, allowing patients to self-administer the medication without visiting a clinic. While this approach offers convenience, ketamine isn’t without risks, and these are exacerbated without medical supervision. If you're considering ketamine therapy and unsure whether to pursue treatment at home or in a clinical setting, this article will break down the key differences, weigh the risks and benefits, and help you make an informed choice.
By Matt Rodriguez July 8, 2025
Living with depression can be incredibly difficult, especially when traditional medications don’t bring relief. In this article, we’ll be discussing the nasal spray, Spravato, which is a breakthrough FDA-approved treatment for depression. We’ll discuss the science and safety of Spravato and what to expect during the treatment process. What Is Spravato? Spravato is a nasal spray containing esketamine , a chemical compound derived from ketamine. Ketamine is a widely recognised, effective, rapid-acting treatment for depression and other mental health disorders that was initially developed as an anesthetic. Esketamine is an enantiomer of ketamine, meaning it is one of two mirror-image molecules that make up ketamine when in its original form (“generic ketamine”). This enantiomer interacts more strongly with NMDA receptors , which are proteins thought to underlie the ketamine’s antidepressant effects. Spravato was developed to treat depression by Janssen Pharmaceuticals , a division of Johnson & Johnson. After rigorous research and clinical testing, Spravato received FDA approval in March 2019 for adults with treatment-resistant depression. In August 2020, it also received approval for adults experiencing depression with acute suicidal ideation or behavior . Unlike ketamine, which is often used “off-label” for various mental health conditions, Spravato is an FDA-approved and regulated treatment. It is administered only in c ertified healthcare settings under a strict protocol to ensure patient safety. How Spravato Works: A Break from Traditional Antidepressants Conventional antidepressants like SSRIs and SNRIs mainly work by changing the levels of certain brain chemicals called monoamines , such as serotonin and norepinephrine. Spravato , however, works differently. It targets a different brain chemical called glutamate , which is essential for overall communication in the brain and functions like learning and memory. Spravato blocks NMDA receptors in the prefrontal cortex , a part of the brain involved in regulating mood and emotions. This boosts glutamate activity in that area, which is thought to be part of the reason why Spravato can relieve depression symptoms so quickly. Spravato also increases neuroplasticity , the brain’s ability to reorganize itself. This helps with depression in three main ways: Synaptic plasticity refers to the brain's ability to reorganize the connections between nerve cells, called synapses. Strengthening these connections may help strengthen circuits involved in stress and emotional regulation. Neurogenesis is the process of creating new nerve cells. This can help repair brain areas affected by depression. Functional connectivity describes how different regions of the brain work together. Improved connectivity may help people escape negative thought patterns and develop healthier, more flexible ways of thinking. Who Is Eligible for Spravato Treatment? Spravato is approved for use in adults diagnosed with TRD. To be considered for TRD, a person must have a formal diagnosis of MDD and must have tried at least two different antidepressants , at the right doses and for a minimum of six months, without significant improvement in symptoms. In addition to TRD, Spravato is also approved for patients experiencing depression with acute suicidal ideation or behavior . The patient will have active suicidal thoughts and intend to harm themselves. To be eligible for Spravato, patients must: Be diagnosed with MDD with TRD or MDSI Be currently taking a standard oral antidepressant (Spravato is used in combination with another medication) Be evaluated and monitored in a certified Spravato treatment center Be free from contraindications such as vascular disease or hemorrhage What to Expect During a Spravato Session Spravato is not a take-home medication. Each treatment must be administered in person at an approved clinic under close medical supervision. At our TMS and Ketamine Clinic of Southwest Florida, we’re a licensed provider of Spravato, serving Fort Myers and the surrounding areas. Here’s what you can expect if you undergo Spravato treatment at our centre: Arrival and Preparation You’ll check in and be escorted to a comfortable, private treatment room. A clinician will review your health status and answer any questions. Administration You’ll use the nasal spray yourself, but under direct observation. The device is pre-measured and easy to use. Monitoring Period After administration, you’ll be monitored for at least two hours . During this time, side effects are observed and managed, and you'll be made as comfortable as possible. Post-Treatment Once cleared by medical staff, you’ll be released to a pre-arranged caregiver or driver. You must not drive or operate heavy machinery for the rest of the day. The initial treatment schedule typically includes two sessions per week for four weeks , followed by a tapering period where the frequency is reduced based on your response. How Is Spravato Different from Ketamine? Although Spravato and ketamine are chemically related and affect the brain in similar ways, there are key differences in how they’re used in clinical practice: Spravato is FDA-approved specifically for depression , while ketamine is used “off-label” for a variety of conditions, including PTSD, anxiety, and chronic pain. Spravato is administered only via nasal spray in a certified clinic, while ketamine can be delivered through IV infusion, intramuscular injection, or oral lozenge . Spravato has a standardized dosage and protocol , ensuring consistency across treatments. Ketamine doses and regimens may vary more widely depending on the provider and purpose. Some patients find ketamine’s dissociative effects more pronounced, which can lead to therapeutic insights but may also be more intense or uncomfortable for others. Both treatments can be effective. If you’re uncertain about which one best suits you, our care team at TMS and Ketamine Clinic of Southwest Florida can help determine the most appropriate option based on your symptoms, history, and goals. What Are the Side Effects of Spravato? While Spravato is generally well-tolerated, it can cause side effects, most of which occur shortly after administration and resolve within a few hours. Common side effects include: Nausea or vomiting Dizziness or lightheadedness Dissociation (feeling disconnected from oneself or surroundings) Headache Increased blood pressure Fatigue or drowsiness Because of these effects, Spravato is administered only under supervision , with patients observed until they are stable and alert. Spravato Clinical Evidence: Effectiveness of Spravato in Depression In a 2018 study , participants with moderate to severe depression symptoms were treated with Spravato. At the final follow-up, 65% of participants had a 50% or greater decrease in scores of depression symptoms . Over 30% also achieved remission , meaning their symptoms had either gone or were very mild. In a more recent study , the effects of Spravato were assessed in 68 patients with MDD at imminent risk of suicide. Spravato led to a significant decrease in suicidal ideation and depression scores compared to the placebo, with noticeable improvement as early as four hours after treatment . Take the First Step Toward Relief At the TMS and Ketamine Clinic of Southwest Florida, we specialize in cutting-edge treatments for depression, including Spravato. Our experienced psychiatrist and dedicated mental health professionals are here to provide compassionate care and support every step of the way. If traditional treatments haven’t helped, you don’t have to keep struggling. Contact us today to find out if our innovative therapies could be the right solution for you.
By Kimberly Mercille May 27, 2025
In recent years, innovative treatments like ketamine and Spravato (esketamine) have emerged as groundbreaking options for individuals struggling with severe depression. Both treatments offer rapid relief, particularly for those who have not found success with traditional therapies. While ketamine and Spravato share similarities, they also have important differences in how they are used, how they work, their safety profiles, and their costs. At SW Florida TMS & Ketamine Clinic , we specialize in providing personalized, effective care to individuals seeking relief from mental health challenges. Understanding the differences between ketamine and Spravato can help you make an informed decision about which treatment is best suited to your needs.
By Matt Rodriguez May 7, 2025
At Southwest Florida TMS and Ketamine Clinic, we understand how difficult it can be to manage severe mental health conditions when traditional treatments aren’t effective. That’s why we specialize in two innovative therapies: Transcranial Magnetic Stimulation (TMS ) and ketamine therapy . In this article, we’ll explore the key similarities and differences between these treatments to help you determine which option may be right for you.
By Matt Rodriguez April 1, 2025
Spravato (esketamine) is a groundbreaking treatment for individuals with treatment-resistant depression (TRD) and major depressive disorder with suicidal ideation (MDSI). Unlike traditional antidepressants, Spravato works rapidly, often providing symptom relief within hours. In this article, we’ll introduce Spravato, discuss how long it takes to work, and explore its short- and long-term effects. What is Spravato and How Does It Work? Spravato (esketamine) is an FDA-approved nasal spray derived from ketamine, specifically designed to treat individuals with TRD and MDSI. Like ketamine, Spravato works by inhibiting NMDA receptors —proteins involved in learning and memory. This inhibition leads to the release of glutamate, a key neurotransmitter, triggering several downstream effects in brain cells. Unlike standard antidepressants, Spravato has rapid-acting effects, sometimes appearing almost immediately after use. It also offers sustained benefits compared to conventional medications and doesn’t require daily use. Short- and Long-Term Effects of Spravato on the Brain Immediate Effects Spravato enhances activity in brain regions responsible for mood regulation, which are often underactive in depression. This effect can occur within hours, often within 24 hours, leading to symptom relief and an improved mood. Long-Term Effects Over time, repeated doses of Spravato strengthen connections between nerve cells through neuroplasticity . Spravato stimulates the production of proteins that support this process, reinforcing neural circuits linked to mood and emotional regulation. Neuroplasticity may explain Spravato’s prolonged improvements in depression. How Long Does It Take for Spravato to Work? Clinical trials have shown that Spravato can quickly reduce symptoms of depression, often within hours or days. In a study of adults with TRD, those who took Spravato along with an antidepressant experienced noticeable symptom relief within 24 hours—an improvement greater than those who took a placebo with an antidepressant. Both groups continued improving over the next 28 days, but the difference between them remained significant. For people with MDSI, clinical studies have shown that Spravato, combined with an antidepressant, significantly reduces symptoms within 24 hours compared to placebo groups. The greatest differences are seen within four hours of taking the medication. Factors That Affect How Long Spravato Takes to Work The time it takes for Spravato to start working varies from person to person. Some may feel relief within hours, while others may require several treatments over days or weeks to notice significant changes. Factors that influence how quickly Spravato works include: Severity of Depression – Those with more severe symptoms may take longer to notice improvement. Individual Brain Chemistry – Differences in neurotransmitter activity can affect response time. Previous Treatments – If someone has had multiple unsuccessful treatments, their response may be slower. Overall Health – Chronic illnesses or nutritional deficiencies may impact treatment effectiveness. Psychological and Environmental Factors – Stress levels, support systems, and therapy participation can all play a role. How Long Do the Effects of Spravato Last? A single dose of Spravato provides relief for up to 24 hours, but for sustained benefits, treatment follows a structured regimen: Induction Phase Twice-weekly doses for the first four weeks. Maintenance Phase Begins after Week 4, with dosing frequency gradually reduced based on clinical response—typically shifting to once weekly or every two weeks. A long-term study found that 35.6% of patients achieved remission after the induction phase , and 46.1% remained in remission during the maintenance phase . On average, patients in the maintenance phase had used Spravato for just over three years, indicating its continued benefits with long-term use. Spravato Short-Term Side Effects While Spravato is generally well tolerated, mild side effects are common, including: Dizziness Nausea Sedation or drowsiness Dissociation (feeling detached from one’s body or reality) Increased blood pressure Anxiety or restlessness Elevated mood or euphoria These side effects typically wear off within a few hours but can linger for up to 24 hours. Safety Considerations Monitoring : Spravato is administered in a certified healthcare setting under medical supervision. Patients are monitored for at least two hours post-dose for potential side effects. Driving Restrictions : Due to possible sedation and dissociation, patients should not drive or operate heavy machinery until the following day after a full night’s rest. Potential Long-Term Risks of Spravato Ketamine is a drug of abuse with addictive properties. Chronic misuse has been linked to long-term effects such as cognitive impairment and damage to the bladder, liver, and kidneys. However, Spravato is administered in a controlled clinical environment, significantly reducing the risk of misuse . While it has not been extensively studied in patients with pre-existing substance abuse disorders, those with addiction histories may be at higher risk. Physically, Spravato appears safe for long-term use , though some evidence suggests users may experience bladder-related symptoms. However, clinical trials have found no significant difference in bladder infections between Spravato and non-Spravato patients. Spravato Treatment at SW Florida TMS & Ketamine Clinic At Southwest Florida TMS & Ketamine Clinic , we specialize in innovative depression treatments , including Spravato therapy for individuals with TRD. If you’re struggling with depression and haven’t found relief from conventional therapy, our services, based in Fort Myers, could have the solution you need. Spravato is a fast-acting medication with sustained benefits, and our team is highly experienced in delivering this medicine with expert care. If you choose to have treatment at our service, we will closely monitor you during and after administration and will be here to provide support after and between doses. For more information on Spravato treatment and to schedule a consultation, visit our Spravato Clinic page . Key Takeaways Rapid Relief: Many patients experience symptom improvement within hours or days of starting Spravato. Mechanism of Action: Spravato enhances mood-regulating brain activity and promotes neuroplasticity. Individual Variability: Factors like depression severity, brain chemistry, and past treatments influence response time. Sustained Benefits: With continued treatment, Spravato strengthens neural connections, supporting long-term depression relief. Safety Considerations: While generally well-tolerated, Spravato requires medical supervision due to potential side effects and driving restrictions. Expert Care at SW Florida TMS & Ketamine Clinic: Offering specialized Spravato therapy with close monitoring and personalized treatment plans for patients with TRD.
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