What Is Spravato and How Does It Work for Depression?

Depression can feel overwhelming, especially when standard medications have not brought enough relief. However, for some patients, after years of trying multiple medications, Spravato can be the first treatment that brings a noticeable shift in mood within days.

At Lonerock Clinic, where whole-person, evidence-based care is central to everything we do, patients often ask about newer treatment options designed specifically for difficult-to-treat depression. One of the most talked-about options is Spravato.

Understanding what Spravato is, how it works in the brain, and when it may be appropriate can help patients and families make informed, confident decisions about care. Spravato is not a replacement for traditional antidepressants, nor is it a first-line treatment. Instead, it represents a carefully regulated, FDA-approved option for adults whose depression has not improved with conventional therapies or who are experiencing acute suicidal thoughts.

This article explains what Spravato is, how it works, what treatment involves, and why it may play an important role in modern depression care when delivered in a supportive, integrated clinical setting like Lonerock Clinic.

What Is Spravato?

Spravato is a prescription nasal spray that contains esketamine, a compound derived from ketamine. It is approved by the U.S. Food and Drug Administration for adults with treatment-resistant depression and for certain adults with major depressive disorder accompanied by acute suicidal thoughts or behaviors. Unlike daily oral antidepressants, Spravato is administered intermittently in a certified medical setting under close supervision.

A key point when asking what is Spravato is understanding that it is always used as part of a broader treatment plan. It is typically combined with an oral antidepressant and ongoing clinical support. Because of its unique effects and safety considerations, Spravato cannot be taken at home and must follow strict monitoring guidelines.

Understanding Esketamine as the Active Ingredient

Esketamine is one part of the ketamine molecule and has specific effects on brain signaling systems involved in mood regulation. Traditional antidepressants mainly influence serotonin, norepinephrine, or dopamine. Esketamine works differently by targeting the glutamate system, which plays a major role in how brain cells communicate, adapt, and form new connections.

When delivered as a nasal spray, esketamine is absorbed through the nasal lining and reaches the brain relatively quickly. This faster onset is one reason Spravato has drawn attention for people who have not responded to standard medications or who need rapid symptom relief under medical supervision.

FDA Approval and Clinical Indications

Spravato received FDA approval after clinical trials showed benefit for adults with depression that had not improved after trying at least two antidepressants at adequate doses and durations. This definition is known as treatment-resistant depression. The FDA also approved Spravato, in combination with an oral antidepressant, for adults with major depressive disorder who are experiencing acute suicidal ideation or behavior.

Because of potential side effects, Spravato is available only through a Risk Evaluation and Mitigation Strategy, commonly called a REMS program. Clinics must be certified, and patients must be monitored carefully during and after each treatment session. These safeguards ensure that Spravato is used responsibly and safely.

How Spravato Is Different From Traditional Antidepressants

One of the most important distinctions when exploring what is Spravato lies in how it differs from standard antidepressants. Most oral antidepressants work gradually and may take several weeks to show noticeable effects. Spravato, by contrast, can lead to symptom improvement within hours or days for some patients.

Traditional medications are taken daily at home, while Spravato is administered in a clinic setting at scheduled intervals. Spravato also has a different side effect profile, including short-term changes in perception, blood pressure, and alertness, which is why monitoring is required. These differences make Spravato a specialized option rather than a routine treatment.

How Spravato Works in the Brain

Spravato’s effects are tied to how it influences glutamate, the brain’s primary excitatory neurotransmitter. By acting on specific receptors, Spravato can trigger changes in neural circuits associated with mood, stress response, and emotional regulation.

The Role of NMDA Receptors

Esketamine interacts with NMDA receptors, which help regulate glutamate activity in the brain. By modulating these receptors, Spravato alters patterns of neural signaling that are often disrupted in severe depression. This modulation sets off a cascade of downstream effects rather than simply blocking brain activity.

These changes can temporarily affect perception and blood pressure, which is why clinicians monitor patients closely during treatment. The goal is to harness the therapeutic benefits of NMDA modulation while maintaining safety.

Glutamate, AMPA Receptors, and Neuroplasticity

When NMDA receptor activity shifts, glutamate levels can briefly increase in certain brain regions. This increase stimulates AMPA receptors, which are linked to synaptic strengthening and neuroplasticity. Neuroplasticity refers to the brain’s ability to form new connections and adapt to new patterns of thinking and behavior.

Increased plasticity may help explain why some patients experience rapid improvements in mood, motivation, or clarity. To support lasting change, clinicians often pair Spravato treatment with psychotherapy and ongoing medication management.

Spravato Compared to Ketamine Infusion Therapy

Spravato and intravenous ketamine therapy share similar mechanisms, but they differ in important ways. IV ketamine typically uses a racemic mixture of ketamine and is often delivered in hospital or infusion center settings. Spravato uses esketamine alone and is administered as a nasal spray in certified outpatient clinics.

The route of administration affects dosing precision, monitoring protocols, and accessibility. While both approaches target glutamate pathways, Spravato follows standardized FDA-approved dosing schedules and safety requirements, making it a structured option for outpatient care.

What to Expect During Spravato Treatment?

Understanding the treatment process is essential when considering what is Spravato and whether it fits your needs. Each session follows a consistent structure designed to maximize safety and therapeutic benefit.

Administration and Monitoring

Spravato is self-administered under the supervision of trained healthcare professionals. Before dosing, clinicians check blood pressure and review current symptoms. After using the nasal spray, patients remain in the clinic for at least two hours of observation.

During this time, staff monitor for sedation, dissociation, changes in blood pressure, or other side effects. Patients are required to arrange transportation home and must avoid driving or operating machinery until the following day.

Treatment Schedule

Most patients begin with an induction phase that involves twice-weekly sessions for several weeks. If improvement is seen, treatment frequency typically decreases to once weekly and then to every two weeks during maintenance. The exact schedule depends on response, tolerability, and clinical judgment.

Safety Considerations and Potential Side Effects

Spravato can cause both short-term and longer-term side effects, which is why careful screening and follow-up are essential.

Common Short-Term Effects

Many patients experience dizziness, nausea, fatigue, or dissociation shortly after dosing. Dissociation may feel like detachment from thoughts, emotions, or surroundings. These effects usually peak within the first hour and resolve the same day.

Temporary increases in blood pressure are common, making monitoring an important part of each visit. Because alertness can be affected, same-day driving restrictions are mandatory.

Serious Risks and Long-Term Monitoring

Spravato carries a risk of respiratory depression, especially when combined with alcohol, opioids, or other sedating medications. For this reason, treatment is limited to certified settings with trained staff.

Long-term safety data are still evolving. Some patients receiving ketamine-related treatments report bladder symptoms or cognitive changes over time. Clinicians regularly reassess the balance of benefits and risks and may adjust or discontinue treatment if concerns arise.

Who May Benefit From Spravato?

Spravato is intended for adults with treatment-resistant depression or those with major depressive disorder and acute suicidal ideation when rapid symptom relief is needed. A comprehensive evaluation is required to determine eligibility, including a review of mental health history, prior treatments, medical conditions, and substance use risk.

At Lonerock Clinic, this evaluation reflects a whole-person approach, ensuring that Spravato is considered within the broader context of physical health, emotional well-being, and long-term goals.

Frequently Asked Questions About Spravato

How quickly does Spravato work for depression?

Some patients notice improvement within hours or days after treatment, while others require several sessions to assess response. Results vary, and Spravato is typically combined with other treatments to support lasting benefits.

Is Spravato the same as ketamine?

Spravato contains esketamine, which is one part of the ketamine molecule. While both affect glutamate pathways, Spravato is FDA-approved, delivered as a nasal spray, and subject to strict safety protocols.

Can Spravato be used long term?

Some patients continue Spravato as maintenance therapy at reduced frequency. Long-term use requires regular evaluation to monitor effectiveness, side effects, and overall health.

Does insurance cover Spravato treatment?

Many insurance plans cover Spravato for FDA-approved indications, but prior authorization is often required. Coverage depends on documented treatment history and plan-specific policies.

Considering Spravato as Part of Whole-Person Care

For individuals living with depression that has not responded to standard treatments, understanding what is Spravato can open the door to new possibilities.

Spravato offers a scientifically grounded, FDA-approved option that works differently from traditional antidepressants and may provide faster relief for some patients.

At Lonerock Clinic, Spravato is part of a comprehensive, compassionate approach to care, thoughtfully combined with therapy and medical support rather than used on its own. By combining advanced treatments with careful monitoring, psychotherapy, and primary care support, the goal is to help patients move toward lasting stability and improved quality of life. 

Anyone considering Spravato should have an open, informed discussion with their care team about whether it fits their unique needs and circumstances.