For people whose depression hasn’t improved with standard medications, Spravato® (esketamine) — part of the ketamine family of treatments, may offer new hope. Unlike traditional antidepressants, which take weeks to work and target serotonin, Spravato acts on a different brain system, one linked to mood, stress, and resilience.
With any new treatment, it’s important to understand what is Spravato? How does it work, and what should patients expect?
What is Spravato?
Spravato, also known as esketamine, is a prescription nasal spray approved by the U.S. Food and Drug Administration (FDA). It is used to treat adults with either:
- Treatment-resistant depression (TRD), depression that hasn’t improved after trying at least two oral antidepressants
- Major depressive disorder (MDD) with suicidal thoughts or behaviors
Spravato is typically given in combination with an oral antidepressant to improve results. It’s designed for people who haven’t felt relief from traditional medications or who need faster improvement in symptoms.
Because Spravato can temporarily affect alertness and blood pressure, it’s administered only in certified clinics under supervision. This allows healthcare providers to monitor each person for safety and comfort during and after treatment.
How does Spravato work?
Spravato works differently than most antidepressants. Instead of focusing on serotonin, it targets glutamate, a chemical messenger involved in communication between brain cells.
More specifically, Spravato blocks a receptor called the NMDA receptor, part of the brain’s glutamate system. This change triggers a series of reactions that strengthen and rebuild neural connections in areas of the brain that regulate mood and emotions.
Many people with depression have reduced activity in these regions. By boosting communication between brain cells, Spravato helps restore balance and support more flexible thinking and emotional regulation.
What makes Spravato unique?
- Rapid action: Some people notice improvement in mood and energy within 24 hours of treatment.
- Different mechanism: It works on glutamate pathways rather than serotonin or dopamine.
- Neuroplasticity support: By helping the brain form new connections, Spravato may improve resilience to stress and negative thought patterns.
While researchers continue to study the exact mechanisms behind its effects, clinical trials have shown that Spravato can reduce depressive symptoms and suicidal thoughts in adults who haven’t responded to other treatments.
Administration and dosage
Spravato is taken as a nasal spray, with each dose administered under the guidance of a healthcare provider.
During each session:
- A medical professional helps guide patients through self-administering the spray; one spray per nostril.
- Patients are monitored for two hours by a care team that monitors their blood pressure and overall well-being.
- Because Spravato can cause drowsiness or dizziness, patients are not allowed to drive or operate heavy machinery. They should arrange a ride home with a loved one or ride-share prior to their treatment sessions.
Treatment typically begins with twice-weekly sessions for the first month, followed by less frequent maintenance doses as symptoms improve. The total number of sessions can vary from patient to patient.
Benefits of Spravato
Spravato can make a meaningful difference for people with difficult-to-treat depression. Key benefits include:
- Rapid symptom relief: Some people feel better within hours or days.
- Reduction in suicidal thoughts: Clinical studies have shown decreases in suicidal ideation among people with MDD.
- Improved mood and function: Many report more energy, motivation, and emotional clarity.
- Adjunctive use: Works alongside traditional antidepressants to enhance their effects.
By offering a new approach to brain chemistry, Spravato helps people who’ve struggled with long-term depression find renewed stability and hope.
Interaction with other medicines
Spravato can interact with other medications, including:
- Antidepressants
- Blood pressure medications
- Sleep aids or sedatives
- Nasal decongestants
These interactions can increase side effects such as drowsiness, dizziness, or elevated blood pressure. Always tell your healthcare provider about every prescription, over-the-counter medicine, or supplement you take.
Providers will review your full medication list before treatment and may adjust timing or dosage to ensure Spravato is used safely.
Side effects of Spravato
Like any medication, Spravato can cause side effects. Most are mild and fade within a few hours. Common Spravato side effects include:
- Feeling lightheaded or dizzy
- Nausea
- Sleepiness or fatigue
- Temporary increases in blood pressure
- Feeling disconnected or “spaced out,” also known as dissociation
Less common but serious side effects may include:
- Trouble breathing or chest discomfort
- Sudden severe headache
- Bladder irritation or pain
- Worsening depression or suicidal thoughts
Because these effects are possible, each session is supervised by a trained healthcare team that can provide immediate support if needed.
Patient eligibility
Spravato is FDA-approved for adults diagnosed with treatment-resistant depression or major depressive disorder with suicidal thoughts or behaviors.
You may be a candidate if:
- You’ve tried at least two antidepressants without significant improvement
- You continue to experience severe or persistent symptoms
- Your provider determines Spravato is safe based on your medical history
Spravato may not be suitable for people with certain conditions, such as:
- Uncontrolled high blood pressure or heart disease
- A history of aneurysms or vascular problems
- Current or past substance misuse
- Pregnancy or breastfeeding
During your consultation, your provider will discuss your health history and current medications to decide if Spravato is the right fit.
Safety and monitoring
Spravato can only be administered in certified clinics that participate in a safety program called the REMS (Risk Evaluation and Mitigation Strategy) program. This ensures proper monitoring, dosing, and follow-up care.
Healthcare providers check vital signs before and after each session, track side effects, and tailor dosing as needed. The goal is to help people feel supported throughout the process: physically, mentally, and emotionally.
Combining Spravato with other treatments
Spravato is most effective when used as part of a comprehensive treatment plan that can include:
- Medication management: Regular psychiatry check-ins help track progress and fine-tune care.
- Therapy: Cognitive-behavioral therapy (CBT) or other evidence-based therapies can strengthen coping skills.
- TMS therapy: For some people, transcranial magnetic stimulation (TMS) can also be effective for depression and anxious depression.
This integrated approach supports lasting progress and overall mental health.
When to seek help
Patients who experience symptoms such as severe dizziness, chest tightness, shortness of breath, or sudden headache after Spravato treatment, should seek medical care immediately.
Reach out to your provider if you notice:
- Worsening depression or anxiety
- Suicidal thoughts
- Persistent side effects that interfere with daily life
Early communication ensures your care team can adjust treatment and keep you safe.
Summary
Spravato offers a new path forward for people living with major depressive disorder or treatment-resistant depression. By working differently in the brain, it can provide faster symptom relief and hope for those who haven’t responded to traditional medications.
Understanding how Spravato works, its benefits, and potential side effects helps people make informed choices about their care and approach treatment with confidence.
Key takeaways
- Spravato (esketamine) is a nasal spray approved by the U.S. Food and Drug Administration (FDA) for adults with treatment-resistant depression or major depressive disorder with suicidal thoughts.
- It works through the brain’s glutamate system, helping restore neural connections that support mood and emotional balance.
- Common side effects include dizziness, nausea, and temporary increases in blood pressure.
- Spravato must be administered in a certified clinic under professional supervision.
- When combined with oral antidepressants, therapy, and psychiatric care, Spravato can offer meaningful relief and improved quality of life.
Looking for Spravato® treatment near you?
Pacific Mind Health offers Spravato® (esketamine) therapy for treatment-resistant depression and major depressive disorder at our Long Beach and Irvine locations. Our experienced clinicians provide compassionate, evidence-based care to help you feel better.
Ready to take the next step? Schedule a consultation today to see if Spravato is right for you.
