Spravato Nasal Spray for Depression

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 certified 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:

  1. 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.
  2. Administration
    You’ll use the nasal spray yourself, but under direct observation. The device is pre-measured and easy to use.
  3. 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.
  4. 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.

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

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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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